Influence of Drug Binding on DNA Hydration: Acoustic and Densimetric Characterizations of Netropsin Binding to the Poly(dAdT).cntdot.Poly(dAdT) and Poly(dA).cntdot.Poly(dT) Duplexes and the Poly(dT).cntdot.Poly(dA).cntdot.Poly(dT) Triplex at 25 .degree.C

Tv, Chalikian; Ge, Plum; Ap, Sarvazyan; Kj, Breslauer

doi:10.1021/bi00195a003

Cited by 103 publications

(81 citation statements)

References 49 publications

(64 reference statements)

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“…The long residence time (nanoseconds) of water molecules detected by NMR (19) is more important for maintaining the structural integrity (structural water), whereas the dynamically ordered water is of more significance to recognition processes such as those involved in ligand (29) or protein (30) binding. The high mobility of water at the interface is critical to the net entropy change of recognition and to making a layer of ''lubricant'' for improving complementarity of recognition by virtue of its almost bulk-like property.…”

Section: Resultsmentioning

confidence: 99%

Site- and sequence-selective ultrafast hydration of DNA

Pal

Zhao

Xia

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

107

137

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Water molecules in the DNA grooves are critical for maintaining structural integrity, conformational changes, and molecular recognition. Here we report studies of site-and sequence-specific hydration dynamics, using 2-aminopurine (Ap) as the intrinsic fluorescence probe and with femtosecond resolution. The dodecamer d[CGCA(Ap)ATTTGCG]2 was investigated, and we also examined the effect of a specific minor groove-binding drug, pentamidine, on hydration dynamics. Two time scales were observed: Ϸ1 ps (bulklike) and 10 -12 ps (weakly bound type), consistent with layer hydration observed in proteins and DNA. However, for denatured DNA, the cosolvent condition of 40% formamide hydration is very different: it becomes that of bulk (in the presence of formamide). Well known electron transfer between Ap and nearby bases in stacked assemblies becomes inefficient in the single-stranded state. The rigidity of Ap in the single strands is significantly higher than that in bulk water and that attached to deoxyribose, suggesting a unique role for the dynamics of the phosphate-sugarbase in helix formation. The disparity in minor and major groove hydration is evident because of the site selection of Ap and in the time scale observed here (in the presence and absence of the drug), which is different by a factor of 2 from that observed in the minor groove-drug recognition.T he influence of hydration on the conformation and interactions of DNA has been the subject of many investigations using x-ray crystallography, NMR, molecular dynamics, and thermodynamic techniques (for recent reviews see refs. 1-4). The important role of water in the three-dimensional structures adopted by DNA is summarized in one of these reviews (1). At the interface between DNA and proteins (5, 6), water molecules in the first hydration shell of DNA ''mark'' the positions where protein residues hydrogen-bond to DNA. Even for specificity of cleavage in DNA, water activity affects site-specific recognition of DNA by EcoRI (6) as it does in protein function (7).In the minor groove of a B-form DNA duplex, hydration and its role in drug binding are striking. In a recent publication (8) from this laboratory, we described how the drug (Hoechst 33258) bound in the minor groove of DNA can be used to probe the dynamics of the water layer. For a DNA dodecamer duplex d(CGCAAATTTGCG) 2 , two well separated hydration times were found: 1.4 and 19 ps, compared with 0.2 and 1.2 ps for the same drug in bulk water. For comparison, we also studied genomic calf thymus DNA for which the hydration exhibits time scales similar to those of the dodecamer DNA.In this study, we use a DNA base analog, 2-aminopurine (Ap), in the same dodecamer B-DNA duplex d(CGCAApATTTGCG) 2 as an intrinsic fluorescence probe. Ap has been shown by NMR spectroscopy and thermodynamic measurements to form a stable base pair with thymine in a DNA oligomer, stabilized by two hydrogen bonds in a Watson-Crick geometry (9, 10) (see Fig. 1). Thus it is reasonable to consider that the modification by Ap does not alte...

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Section: Resultsmentioning

confidence: 99%

Site- and sequence-selective ultrafast hydration of DNA

Pal

Zhao

Xia

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

107

137

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“…1,9 Polyamides displace the spine of hydration in a multidentate fashion by forming hydrogen bonds from each amide NH to proximal purine N3 and pyrimidine O2 atoms, 1,12,13 which provides a large entropic driving force for binding. 14 The narrow minor groove of A-tracts accommodates netropsin and distamycin in a 1:1 complex well, but the plasticity of T-A steps is required in order to expand the minor groove for accommodation of two ligands. 2,10 The X-ray structure of netropsin bound as a 1:1 complex to DNA inspired the lexitropsin model, where it was predicted that replacing one or both Py residues in netropsin with N-methylimidazolecarboxamide (Im) would confer G·C recognition by simultaneously alleviating a steric interaction with the C3-H of Py and forming a hydrogen bond from Im-N3 to G-NH2.…”

Section: Introductionmentioning

confidence: 99%

Structure of a β-Alanine-linked Polyamide Bound to a Full Helical Turn of Purine Tract DNA in the 1:1 Motif

Urbach

Love

Ross

et al. 2002

Journal of Molecular Biology

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Polyamides composed of N-methylpyrrole (Py), N-methylimidazole (Im) and N-methylhydroxypyrrole (Hp) amino acids linked by b-alanine (b) bind the minor groove of DNA in 1:1 and 2:1 ligand to DNA stoichiometries. Although the energetics and structure of the 2:1 complex has been explored extensively, there is remarkably less understood about 1:1 recognition beyond the initial studies on netropsin and distamycin. We present here the 1:1 solution structure of ImPy -b -Im-b -ImPy -b-Dp bound in a single orientation to its match site within the DNA duplex 5 0 -CCAAAGAGAAGCG-3 0 ·5 0 -CGCTTCTCTTTGG-3 0 (match site in bold), as determined by 2D 1 H NMR methods. The representative ensemble of 12 conformers has no distance constraint violations greater than 0.13 Å and a pairwise RMSD over the binding site of 0.80 Å . Intermolecular NOEs place the polyamide deep inside the minor groove, and oriented N -C with the 3 0 -5 0 direction of the purine-rich strand. Analysis of the high-resolution structure reveals the ligand bound 1:1 completely within the minor groove for a full turn of the DNA helix. The DNA is B-form (average rise ¼ 3.3 Å , twist ¼ 388) with a narrow minor groove closing down to 3.0-4.5 Å in the binding site. The ligand and DNA are aligned in register, with each polyamide NH group forming bifurcated hydrogen bonds of similar length to purine N3 and pyrimidine O2 atoms on the floor of the minor groove. Each imidazole group is hydrogen bonded via its N3 atom to its proximal guanine's exocyclic amino group. The important roles of b-alanine and imidazole for 1:1 binding are discussed.

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“…Various techniques are available to study hydration changes accompanying ligand-DNA interaction 31,32) and osmotic stress approach has gained importance due to its ability to specifically alter water activity of the surrounding solution; a fact that has been harnessed to measure forces between molecules. 31,32) It is relatively a simple technique to study the hydration changes upon ligand-DNA interaction and gives stoichiometric amount of water release or uptake upon biomolecular complexation.27) The principle of osmotic stress method is based on Gibbs-Duhem equation. 34,35) The neutral solutes are added directly to the solution containing the ligand and macromolecule causes changes in the water activity of the solution.…”

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confidence: 99%

Osmolyte Changes the Binding Affinity and Mode of Interaction of Minor Groove Binder Hoechst 33258 with Calf Thymus DNA

Anuradha

Alam

Chaudhury

2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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The bis-benzimidazole molecule Hoechst 33258 ( Fig. 1) is an important DNA minor groove binding ligand.1) Interaction of Hoechst 33258 has been extensively studied using oligonucleotides.2-5) Different aspects of this interaction viz., physicochemical, thermodynamics, NMR, X-ray crystallography, in silico simulation are now well established. 3,[6][7][8][9][10][11] From the classical observation on the ability of Hoechst 33258 binding in the AT rich region of minor groove of DNA. Synthetic chemists have designed various DNA minor groove binders for possible applications such as anticancer, antiviral, and other diseases. 12,13) Studies at cellular level have demonstrated the desired biological effects.14-16) New applications are emerging from studies related to radiosensitization and radioprotection in relation to modification of radiation response by Hoechst derivatives. [17][18][19][20][21] Attempts have also been made to correlate these observations with different Hoechst analogues.Physicochemical and thermodynamic studies have revealed important details on the mechanism of Hoechst 33258-DNA interaction. 12,[22][23][24] Role of water surrounding DNA has emerged as an important entity in the interaction processes. 12,22,25) The network of newly formed hydrogen bonds between the ligand and DNA replaces previously existing direct solute-solvent (water) hydrogen bonds in the minor groove. Hydration changes strongly influences the thermodynamics of ligand-DNA interaction. The change in hydration after the complex formation appeared to be governed by the structure of the ligand. 3,[26][27][28][29] Most of the studies and hence our understandings are still based on oligonucleotides. 5,27,30) Water molecules located close to the binding surfaces are more structured than those of bulk solvent. These locally structured water molecules are retained or released during a binding process with different thermodynamic consequences. Various techniques are available to study hydration changes accompanying ligand-DNA interaction 31,32) and osmotic stress approach has gained importance due to its ability to specifically alter water activity of the surrounding solution; a fact that has been harnessed to measure forces between molecules. 31,32) It is relatively a simple technique to study the hydration changes upon ligand-DNA interaction and gives stoichiometric amount of water release or uptake upon biomolecular complexation.27) The principle of osmotic stress method is based on Gibbs-Duhem equation. 34,35) The neutral solutes are added directly to the solution containing the ligand and macromolecule causes changes in the water activity of the solution. Osmotic stress method has been employed for studying the hydration changes for minor groove binder as well as for intercalators. 5,26,27,[36][37][38] In living system, small molecules interact with DNA in a very crowded environment. The presence of co-solutes in the in-vivo conditions affects the interaction process therefore it is important to study the interaction of Hoechst 33258...

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Influence of Drug Binding on DNA Hydration: Acoustic and Densimetric Characterizations of Netropsin Binding to the Poly(dAdT).cntdot.Poly(dAdT) and Poly(dA).cntdot.Poly(dT) Duplexes and the Poly(dT).cntdot.Poly(dA).cntdot.Poly(dT) Triplex at 25 .degree.C

Cited by 103 publications

References 49 publications

Site- and sequence-selective ultrafast hydration of DNA

Site- and sequence-selective ultrafast hydration of DNA

Structure of a β-Alanine-linked Polyamide Bound to a Full Helical Turn of Purine Tract DNA in the 1:1 Motif

Osmolyte Changes the Binding Affinity and Mode of Interaction of Minor Groove Binder Hoechst 33258 with Calf Thymus DNA

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